Role of Hexokinase and VDAC in Neurological Disorders

Title:Role of Hexokinase and VDAC in Neurological Disorders

Volume: 9

Author(s): José César Rosa and Marcelo de Cerqueira César

Affiliation:

Keywords: Energy metabolism, glycolysis, hexokinase, lactate, neurons, VDAC.

Abstract: Several neurological diseases such as bipolar disorders and schizophrenia are linked to impaired brain energy metabolism. A key feature of brain bioenergetics is hexokinase (HK) binding to the outer mitochondrial membrane through the voltage dependent anion channel (VDAC). This has metabolic consequences, with phosphorylation of glucose by mitochondrially bound hexokinase being closely coupled to production of substrate ATP by intramitochondrial oxidative phosphorylation. Additionally, binding of HK to mitochondria inhibits Bax-induced cytochrome c release and apoptosis. Moreover VDAC1 expression level is elevated in cerebellum of patients with Down ´s syndrome, while in Alzheimer ´s disease, VDAC1 levels are decreased in frontal cortex and VDAC2 elevated in temporal cortex. Thus, understanding the roles of VDAC and HK, either separate or interacting in brain, provides new opportunities and challenges to elucidate pathophysiological mechanisms for future therapeutic strategies.

Cite this article as:

Rosa César José and César de Cerqueira Marcelo, Role of Hexokinase and VDAC in Neurological Disorders, Current Molecular Pharmacology 2016; 9 (4) . https://dx.doi.org/10.2174/1874467209666160112123036